Novel 1,3-disubstituted 8-(1-benzyl-1H-pyrazol-4-yl) xanthines: High affinity and selective A2B adenosine receptor antagonists

Journal of Medicinal Chemistry

Volumn 49, Issue 12, 2006, Pages 3682-3692

  Kalla, Rao V ^a   Elzein, Elfatih ^a   Perry, Thao ^a   Li, Xiaofen ^a   Palle, Venkata ^a   Varkhedkar, Vaibhav ^a   Gimbel, Arthur ^a   Maa, Tennig ^a   Zeng, Dewan ^a   Zablocki, Jeff ^a  

^a CV THERAPEUTICS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,3 DIPROPYL 8 (1H PYRAZOL 4 YL) 1H PURINE 2,6(3H,7H) DIONE; 1,3 DIPROPYLXANTHINE DERIVATIVE; 8 (1 BENZYL 1H PYRAZOL 4 YL) 1,3 DIPROPYL 1H PURINE 2,6(3H,7H) DIONE; 8 (1 BENZYL 1H PYRAZOL 4 YL)XANTHINE DERIVATIVE; 8 [1 (3 FLUOROBENZYL) 1H PYRAZOL 4 YL] 1,3 DIPROPYL 1H PURINE 2,6(3H,7H) DIONE; 8 [1 [2 CHLORO 5 (TRIFLUOROMETHYL)BENZYL] 1H PYRAZOL 4 YL] 1,3 DIPROPYL 1H PURINE 2,6(3H,7H) DIONE; 8 [1 [3 (TRIFLUOROMETHYL)BENZYL] 1H PYRAZOL 4 YL] 1,3 DIMETHYL 1H PURINE 2,6(3H,7H) DIONE; 8 [1 [3 (TRIFLUOROMETHYL)BENZYL] 1H PYRAZOL 4 YL] 1,3 DIPROPYL 1H PURINE 2,6(3H,7H) DIONE; ADENOSINE A1 RECEPTOR; ADENOSINE A2 RECEPTOR ANTAGONIST; ADENOSINE A2A RECEPTOR; ADENOSINE A2B RECEPTOR; ADENOSINE A3 RECEPTOR; ALKYL GROUP; BENZYL DERIVATIVE; BUTANE; ETHANE; METHYL GROUP; PHENYL GROUP; PYRAZOLE DERIVATIVE; UNCLASSIFIED DRUG; XANTHINE DERIVATIVE;

ANIMAL CELL; ARTICLE; ASTHMA; BINDING AFFINITY; BRONCHUS HYPERREACTIVITY; CELL STRAIN HEK293; CHO CELL; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; NONHUMAN; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION;

ANIMALS; CELL LINE; CRICETINAE; CRICETULUS; HUMANS; PYRAZOLES; RADIOLIGAND ASSAY; RECEPTOR, ADENOSINE A2B; THEOPHYLLINE; XANTHINES;

EID: 33745169671     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm051268+     Document Type: Article

References (30)

1. Fredholm, B. B.; Ijzerman, A. P.; Jacobson, K. A.; Klotz, K.-N.; Linden, J. International union of pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol. Rev. 2001, 53, 527-552.
2. Polosa, R. Adenosine receptor subtypes: their relevance to adenosine-mediated responses in asthma and chronic obstructive pulmonary disease. Eur. Respir. J. 2002, 20, 488-496.
3. (a) Driver, A. G.; Kukoly, C. A.; Ali, S.; Mustafa, S. J. Adenosine in brachoalveolar lavage fluid in asthma. Am. Rev. Respir. Dis. 1993, 148, 91-97.
4. (b) Huszár, É.; Vass, G.; Vizi, É.; Csoma, Z.; Barát, E.; Molnár Világos, G.; Herjavecz, I.; Horváth, I. Adenosine in exhaled breath condensate in healthy volunteers and in patients with asthma. Eur. Respir. J. 2002, 20, 1393-1398.
5. 2B-mediated process involving Th2 cytokines IL-4 and IL-13 with implications for asthma. J. Immunol. 2004, 172, 7726-7733.
6. 2B adenosine receptors increase cytokine release by bronchial smooth muscle cells. Am. J. Respir. Cell Mol. Biol. 2004, 30, 118-125.
7. 2B receptors in a recombinant system and in peripheral blood cells using a novel selective antagonist radioligand, [3H]MRE 2029-F20. Mol. Pharmacol. 2005, 67, 2137-2147.
8. 2B receptors. Pharmacol. Rev. 1997, 49, 381-402.
9. 2B receptors: a novel therapeutic target in asthma? Trends Phamacol. Sci. 1998, 19, 148-153.
10. 2B receptor as a novel therapeutic target in asthma. Br. J. Pharmacol. 2005, 145, 1009-1015.
11. Stine, R. J.; Marcus, R. H.; Parvin, C. A. Aminophylline loading in asthmatic patients: a protocol trial. Ann. Emerg. Med. 1989, 18, 640-646.
12. D'Alonzo, G. E. Theophylline revisited. Allergy Asthma. Proc. 1996, 17, 335-339.
13. Powell, E. C.; Reynolds, S. L.; Rubenstein, J. S. Theophylline toxicity in children: a retrospective review. Pediatr. Emerg. Care 1993, 9, 129-133.
14. 2B adenosine receptors. Drug Dev. Res. 1999, 47, 45-53.
15. 2B) of 9700 nM, 70 nM, and 16 nM respectively under our assay conditions.
16. 1 adenosine receptors. J. Med. Chem. 1992, 35, 924-930.
17. 2-adenosine receptors. J. Med. Chem. 1985, 28, 487-492.
18. 2B adenosine receptor. Drug Dev. Res. 1999, 47, 178-188.
19. 2B adenosine receptors. J. Med. Chem. 2000, 43, 1165-1172.
20. 1-Adenosine receptor antagonists. Expert Opin. Ther. Pat. 1997, 7, 419-440.
21. 2B adenosine receptors. Curr. Top. Med. Chem. 2003, 3, 427-443.
22. 2A Adenosine Receptor Antagonists. Curr. Top. Med. Chem. 2003, 3, 403-411.
23. 2B receptors. Bioorg. Med. Chem. 2003, 11, 77-85.
24. 3 receptor subtypes. J. Med. Chem. 1998, 41, 2835-2845.
25. 2B receptors. Biochem. Pharmacol. 2004, 68, 305-312.
26. 2B receptor. J. Med. Chem. 2001, 44, 170-179.
27. 2B adenosine receptor antagonists. U.S. Patent 6825349, 2004; WO 0342214, 2003.
28. 2B adenosine receptor antagonists, 227th National Meeting of the American Chemical Society, Anaheim, CA, Mar 28-Apr 1, 2004, MEDI-253.
29. 2B adenosine receptor antagonists. Bioorg. Med. Chem. Lett. 2006, 16, 302-306.
30. 2B adenosine receptor antagonists. J. Med. Chem. 2004, 47, 1434-1447.